Orotidine 5′-monophosphate decarboxylase (OMP decarboxylase) catalyzes the final reaction in pyrimidine nucleotide biosynthesis, converting OMP to uridine 5′-monophosphate (UMP). In eukaryotes, this enzyme also performs the next-to-last step of linking phosphoribosyl-pyrophosphate (PRPP) to orotate to form OMP (Reyes and Guganig (1975) J Biol Chem 250:5097-108; Traut et al. (1980) Biochemistry 19:6062-8). The enzyme is a target for feedback inhibition wherein UTP and UMP both reduce its activity. In prokaryotes, in contrast, there is no feedback inhibition, and the last two enzymatic reactions are not coupled.
Nucleotides are required for the synthesis of DNA and RNA, and are indirectly responsible for protein synthesis, due to the requirement for ribosomes and tRNAs in translation. Therefore, pyrimidine biosynthesis is a key metabolic pathway in all eukaryotes. Manipulation of this pathway is nevertheless possible since mutations to key enzymes can be partially overcome by feeding cells having potentially lethal mutations with CTP, UTP, or their mono- or diphosphate derivatives. Inhibitors of OMP decarboxylase have been identified which vary in their efficacy among different organisms, implying that engineering of the active site may yield enzymes that are more or less sensitive to inhibition (Shostak and Jones (1992) Biochemistry 31:12155-61). It is believed that overexpression or inhibition of OMP decarboxylase in plants may be useful for enhancing growth rates, developing new herbicides, developing new fungicides, developing new insecticides, or selectively altering development of individual organs.